items, such as storybooks and coloring books, should always be designated for single patient use and should be disposed of if they become grossly contaminated or when the child is discharged.

Terminal cleaning, following the discharge of the patient, should include the walls, ceiling, baseboards and floors. Mattresses should be covered with vinyl or other impermeable surface that allows culturing and cleaning without soiling, and be frequently inspected for cracks in their surfaces. At our institution we use air filters with 99.99% efficiency on 0.3 micron sized particles. They are changed regularly, cultured if clinically indicated by infection control monitoring.

All major burned patients should be housed within individual, self-contained positive pressure isolation rooms. However, common areas exist even within these units, predominantly the bathing or showering facilities. These areas should be conscientiously cleansed between patients with an effective bactericidal agent specifically directed at the bacteria, which are common to an individual unit.

Pharmacological considerations in the treatment of burn infections

The timely and effective use of antimicrobials has revolutionized burn care by decreasing invasive wound infections. The untreated burn wound rapidly becomes colonized with bacteria and fungi because of the loss of normal skin barrier mechanisms. As the organisms proliferate to high wound counts ( > 105 organisms per gram of tissue), they may penetrate into viable tissue. Organisms then invade blood vessels, causing a systemic infection that often leads to the death of the patient. This scenario has become uncommon in most burn units because of the effective use of antibiotics and wound care techniques. The antimicrobials that are used can be divided into those given topically and those given systemically.

Topical antimicrobial treatment

Available topical antibiotics can be divided into two classes: salves and soaks. Salves are generally applied directly to the wound with cotton dressings

placed over them, and soaks are generally poured into cotton dressings on the wound. Each of these classes of antimicrobials has advantages and disadvantages. Salves may be applied once or twice a day but may lose their effectiveness between dressing changes. Frequent dressing changes can result in shearing with loss of grafts or underlying healing cells. Soaks remain effective because antibiotic solution can be added without removing the dressing; however, the underlying skin can become macerated.

Topical antibiotic salves include 11% mafenide acetate (Sulfamylon), 1% silver sulfadiazine (Silvadene), polymyxin B, neomycin, bacitracin, mupirocin, and the antifungal agent nystatin. No single agent is completely effective, and each has advantages and disadvantages. Silver sulfadiazine is the most commonly used. It has a broad spectrum of activity because its silver and sulfa moieties cover gram-positive, most gram-negative, and some fungal forms. Some Pseudomonas species possess plas- mid-mediated resistance. Silver sulfadiazine is relatively painless on application, has a high patient acceptance, and is easy to use. Occasionally, patients complain of a burning sensation after it is applied, and, in a few patients, a transient leukopenia develops 3 to 5 days following its continued use. This leukopenia is generally harmless and resolves with or without treatment cessation.

Mafenide acetate is another topical agent with a broad spectrum of activity owing to its sulfa moiety. It is particularly useful against resistant Pseudomonas and Enterococcus species. It also can penetrate eschar, which silver sulfadiazine cannot. Disadvantages include painful application on skin, such as in second-degree wounds. It also can cause an allergic skin rash, and it has carbonic anhydrase inhibitory characteristics that can result in a metabolic acidosis when applied over large surfaces. For these reasons, mafenide sulfate is typically reserved for small full-thickness injuries.

Petroleum-based antimicrobial ointments with polymyxin B, neomycin, and bacitracin are clear on application, painless, and allow for easy wound observation. These agents are commonly used for treatment of facial burns, graft sites, healing donor sites, and small partial-thickness burns. Mupirocin is a relatively new petroleum-based ointment that has

improved activity against gram-positive bacteria, particularly methicillin-resistant S. aureus and selected gram-negative bacteria. Nystatin either in a salve or powder form can be applied to wounds to control fungal growth. Nystatin-containing ointments can be combined with other topical agents to decrease colonization of both bacteria and fungus. The exception is the combination of nystatin and mafenide acetate; each inactivates the other.

Available agents for application as a soak include 0.5% silver nitrate solution, 0 025% sodium hypochlorite (Dakin’s), 0.25% acetic acid, and mafenide acetate as a 5% solution. Silver nitrate has the advantage of being painless on application and having complete antimicrobial effectiveness. The disadvantages include its staining of surfaces to a dull gray or black when the solution dries. This can become problematic in deciphering wound depth during burn excisions and in keeping the patient and his or her surroundings clean of the black staining. The solution is hypotonic as well, and continuous use can cause electrolyte leaching, with rare methemoglobinemia as another complication. A new commercial dressing containing biologically potent silver ions (Acticoat) that are activated in the presence of moisture is available. This dressing holds the promise to retain the effectiveness of silver nitrate without the problems of silver nitrate soaks.

Dakin’s solution (0.25% sodium hypochlorite) has effectiveness against most microbes; however, it also has cytotoxic effects on the healing cells of patients’ wounds. Low concentrations of sodium hypochlorite (0 025%) have less cytotoxic effects while maintaining most of the antimicrobial effects. Hypochlorite ion is inactivated by contact with protein, so the solution must be continually changed. The same is true for acetic acid solutions, which may be more effective against Pseudomonas. Mafenide acetate soaks have the same characteristics of the mafenide acetate salve, except in liquid form.

Systemic antimicrobial treatment (Table 3)

The major role of an antibiotic is to help the body eliminate an agent of infection in a burn patient. Systemic antimicrobial treatment must be thoughtfully considered in the care of the burn patient to prevent the emergence of resistant organisms. The burn

wound will always be colonized with organisms until wound closure is achieved and administration of systemic antimicrobials will not eliminate this colonization but rather promote emergence of resistant organisms. The treatment of an infection is often begun based on empiric knowledge of the most common types of microbial infections seen in the burn population and the antimicrobial agents that are most efficacious in their treatment. If antimicrobial therapy is indicated to treat a specific infection, it should always be based on wound cultures that specifically identify the infecting organism, the colony counts and the sensitivity of that organism to specific antibiotics. Pathology studies of wound biopsies give us information on how invasive the infecting organism is in the body. A pharmaco-therapeutic regimen of antibiotics should follow known parameters about specific burn wound infections in order to potentiate each antibiotic agent’s mechanism of action and pharmacokinetics while decreasing its side effects and systemic toxicities. Also, if antibacterial treatment is necessary, awareness should be heightened for the possibility of superinfection with resistant organisms, yeasts, or fungi. Systemic antimicrobials are indicated to treat documented infections, such as pneumonia, bacteremia, wound infection, and urinary tract infection. Empiric antimicrobial therapy to treat fever should be strongly discouraged because burn patients often have fever secondary to the systemic inflammatory response to burn injury. Prophylactic antimicrobial therapy is recommended only for coverage of the immediate perioperative period surrounding excision or grafting of the burn wound when if is used to cover the documented increase in risk of transient bacteremia. Treatment should be started immediately prior to the procedure and generally discontinued within 24h, assuming restoration of normal cardiovascular hemodynamics.

Gram-positive bacterial infections

The three most common gram-positive organisms responsible for burn wound infections are streptocococci, staphylococci, and enterococci.

Streptococcal infections

-hemolytic streptococci of group A or B (Str. Pyogenes or Str. Agalactiae) are most commonly seen in the first 72 hours post-burn. Cellulitis may develop due to streptococcal infections and usually respond to treatment with natural penicillins or first generation cephalosporins. The natural penicillins that consist of penicillin G and penicillin V and the first generation cephalosporins are bactericidal in action. Like many other -lactam antibiotics, the antibacterial action results from inhibition of mucopeptide synthesis in the bacterial cell wall. Resistance to these antibiotics is caused by the production of -lactamases and/or intrinsic resistance. -lactamase enzymes inactivate these antibiotics by hydrolyzing their -lactam ring. Intrinsic resistance can result from the presence of a permeability barrier in the outer membrane of an infecting organism or alteration in the properties of target enzymes (penicillin-binding proteins). In case of resistance or tolerance to natural penicillins or first

generation cephalosporins, culture and sensitivity data should be utilized to appropriately treat the streptococcal infection.

Staphylococcal infections

Staphylococcus aureus and Staphylococcus epidermidis are natural pathogens found on human skin and therefore the leading cause of infections in burn populations. With their ability to generate penicillinases these microbes break the penicillin -lactam ring and make natural pencillins ineffective against these bacteria.

These types of infections are treated with peni- cillinase-resistant penicillins if they are termed “methicillin sensitive”. These antibiotics included the parenteral antibiotics, nafcillin, methicillin, and oxacillin and the oral antibiotics, cloxacillin, dicloxacillin, nafcilllin and oxacillin. The penicillinase-re- sistant penicillins have a mechanism of action that is similar to other penicillins. They interfere with bac-

terial cell wall synthesis during active multiplication by binding to one or more of the penicillin-binding proteins. They inhibit the final transpeptidation step of peptidoglycan synthesis causing cell wall death and resultant bactericidal activity against susceptible bacteria. However, the Staphylococcal bacteria resistance pattern has become such that these peni- cillinase-resistant penicillin are no longer very effective against these organisms. Staphylococcal infections that are resistant to penicillinase-resistant penicillins are termed MRSA (methicillin resistant Staphylococcus aureus) or MRSE (methicillin-resist- ant Staphylococcus epidermidis).

Vancomycin alone or in combination with other antibiotics has been considered the treatment of choice for infections caused by methicillin-resistant staphylococci. Currently, 100% of all Staphylococcal isolates are susceptible to vancomycin at our hospital. Vancomycin is bactericidal and appears to bind to the bacterial cell wall, causing blockage of glycopeptide polymerization. This effect, which occurs at a site different from that affected by the penicillins, produces immediate inhibition of cell wall synthesis and secondary damage to the cytoplasmic membrane [32]. Vancomycin, however, is a time-de- pendent antimicrobial that requires that the serum level of this drug must remain at all times above the minimum inhibitory concentration (MIC) in order to provide adequate bactericidal activity.

The hypermetabolic burn patient exhibits an increased glomerular filtration rate and increased excretion of the renally cleared drug, vancomycin. Because of the wide interpatient variability of vancomycin elimination in a burn patient, the dosage must be individualized in order to provide an optimal time-dependent serum concentration. The peak and trough levels are derived from the MIC for a particular bacterial organism. The therapeutic peak level is approximately equivalent to 5–8 times the MIC and the trough concentration is equivalent to 1–2 times the MIC. The so-called therapeutic range most often quoted for vancomycin monitoring is peak levels of 30–40mcg/ml and trough levels of 5–10mcg/ml. Because vancomycin is a concentration independent, or time-dependent, antibiotic and because there are practical issues associated with determining a precise peak serum concentration with this multi-compartment antibiotic, most clini-

cians have abandoned the routine practice of determining peak serum concentrations.

The overall AUC/MIC value may be the pharmacodynamic parameter that best correlates with a successful outcome associated with the use of vancomycin, Prolonged exposure to serum levels close to the MIC are associated with the emergence of resistance; therefore it is important to maintain adequate serum concentrations in patients with fast or rapidly changing creatinine clearance such as burn patients. There are also certain body compartments in which penetration is poor, such as the lung and the CNS. It would, also, seem prudent to keep concentrations from being suboptimal in patients with pneumonia or meningitis, as well as in patients receiving dialysis for renal failure. The American Thoracic Society recently published guidelines for hos- pital-acquired, ventilator associated, and health care-associated pneumonia. These guidelines recommend vancomycin in concentrations of 15–20mcg/ml for the treatment of methicillin-resist- ant Staphylococcus aureus pneumonia [33]. These higher concentrations may be needed for sequestered infections or in situations where vancomycin penetration has been documented to be poor. Some clinicians recommend that these higher concentrations of vancomycin may be necessary in the treatment of staphylococcal infections as well.

In the burn patient, vancomycin is often used not only in combination with other ototoxic and nephrotoxic agents such as aminoglycosides, the loop diuretic, furosemide and the antifungal drug, amphotericin. Nephrotoxicity is manifested by transient elevations in the serum blood urea nitrogen (BUN) or serum creatinine and decreases in the glomerular filtration rate and creatinine clearance. Hyaline and granular casts and albumin may also be found in the urine.

Vancomycin should only be administered by slow intravenous infusions as this drug can cause an anaphylactoid reaction known as “Red Man’s Syndrome”. This reaction is characterized by a sudden decrease in blood pressure, which can be severe and may be accompanied by flushing and/or a maculopapular or erythematous rash on the face, neck, chest, and upper extremities; the latter manifestation may also occur in the absence of hypotension. Since this is not a true “allergic reaction”, the patient